Abstract

Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to
cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism,
it is evident that insulin resistance also affects pancreatic β-cells. To directly examine the alterations that occur in islet
morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy
from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion,
and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that
resulted in an altered β-cell–to–α-cell area in the insulin- resistant group. Our data in this series of studies suggest that
neogenesis from duct cells and transdifferentiation of α-cells are potential contributors to the β-cell compensatory response
to insulin resistance in the absence of overt diabetes.